GABAergic projection from nucleus accumbens to ventral pallidum mediates dopamine-induced sensorimotor gating deficits of acoustic startle in rats.
Previous studies have demonstrated that increased mesolimbic dopamine (DA) activity disrupts sensorimotor gating as measured by prepulse inhibition (PPI) of the acoustic startle response (ASR) in rats. Other behavioral changes following mesolimbic DA activation are mediated through GABAergic efferent projections from the nucleus accumbens (NAC) to the ventral pallidum (VP). In this experiment, we examined whether PPI deficits in rats following mesolimbic DA activation are mediated through these same GABAergic substrates. PPI was significantly disrupted in rats following infusion of DA (40 micrograms) into the NAC, and this effect was reversed by infusion of a low dose (10 ng) of the GABA agonist muscimol into the VP. In a second experiment, we tested the hypothesis and the loss of PPI following intra-NAC DA infusion results from a disruption of GABAergic activity within the VP. Consistent with this hypothesis, infusion of the GABA antagonist picrotoxin (0-0.2 micrograms) into the VP caused a significant loss of PPI. These findings strongly suggest that the accumbens-ventral pallidal GABAergic circuitry is a substrate for the decrease in sensorimotor gating induced by mesolimbic DA overactivity.
Swerdlow
N R
NR
Department of Psychiatry, School of Medicine, University of California, San Diego, La Jolla 92093.
Braff
D L
DL
Geyer
M A
MA
D000161:Acoustic Stimulation; D000818:Animals; D004298:Dopamine / Q000502:physiology*; D005917:Globus Pallidus / Q000502:physiology*; D008297:Male; D009434:Neural Pathways / Q000502:physiology; D009714:Nucleus Accumbens / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D013216:Reflex, Startle / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D005680:gamma-Aminobutyric Acid; D004298:Dopamine